Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of ...the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.
Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and ...selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients' admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology.
A novel online coupling of microchip isotachophoresis (μITP) with surface-enhanced Raman spectroscopy (SERS) for the analysis of complex samples is presented. Polymeric microchip with coupled ...channels was used for μITP-SERS analysis of four structurally similar Raman active synthetic dyes (brilliant black BN, carmoisine, ponceau 4R, and sunset yellow FCF) in pharmaceuticals. The μITP separation and simultaneous pre-concentration of the analytes were performed in the first channel of the microchip at pH 6.0 with the aid of non-Raman active discrete spacers (acetate, butyrate, glutarate, pantothenate, and valerate). Silver nanoparticles used for Raman enhancement were present in the second channel, and individual SERS spectra of the dyes were acquired by a mini Raman spectrometer operating at 532 nm. The analytical enhancement factors for silver nanoparticles were 1–5 × 10
4
. The microchip with coupled channels enabled independent μITP separation and SERS detection, and eliminated any adverse impact of nanoparticles on the separation. The developed approach allowed reliable online SERS identification and detection of dyes with limits of detection ranging from 12 to 62 nM. Synthetic dyes were successfully separated, identified, and quantified in pharmaceutical preparations within 7 min without the need for complex or time-consuming sample pretreatment. The results were in good agreement with those obtained by an independent analytical method reported for studied dyes.
Graphical abstract
Biologically active taxanes, present in small- to medium-sized evergreen conifers of various
species, are widely used for their antioxidant, antimicrobial and anti-inflammatory effects, but mostly ...for their antitumour effects used in the treatment of solid tumours of the breast, ovary, lung, bladder, prostate, oesophagus and melanoma. More of the substances found in
plant extracts have medical potential. Therefore, at the beginning of this review, we describe the methods of isolation, identification and determination of taxanes in different plant parts. One of the most important taxanes is paclitaxel, for which we summarize the pharmacokinetic parameters of its different formulations. We also describe toxicological risks during clinical therapy such as hypersensitivity, neurotoxicity, gastrointestinal, cardiovascular, haematological, skin and renal toxicity and toxicity to the respiratory system. Since the effect of the drug-form PTX is enhanced by various
spp. extracts, we summarize published clinical intoxications and all fatal poisonings for the
plant. This showed that, despite their significant use in anticancer treatment, attention should also be focused on the risk of fatal intoxication due to ingestion of extracts from these plants, which are commonly found in our surroundings.
An online coupling of microchip isotachophoresis (µITP) with ion mobility spectrometry (IMS) using thermal evaporation interface is reported for the first time. This combination integrates ...preconcentration power of the µITP followed by unambiguous identification of trace compounds in complex samples by IMS. Short-chain carboxylic acids, chosen as model analytes, were first separated by the µITP in a discontinuous electrolyte system at pH 5–6, and subsequently evaporated at 130 °C during their transfer to the IMS analyzer. Various parameters, affecting the transfer of the separated sample components through the evaporation system, were optimized to minimize dispersion and loss of the analytes as well as to improve sensitivity. The following analytical attributes were obtained for carboxylic acids in the standard solutions: 0.1–0.3 mg L−1 detection limits, 0.4–0.9 mg L−1 quantitation limits, linear calibration range from the quantitation limit to 75 mg L−1, 0.2–0.3% RSD of the IMS response and 98–102% accuracy. The analytical potential of the developed µITP-IMS combination was demonstrated on the analysis of various food, pharmaceutical and biological samples, in which the studied acids are naturally present. These include: apple vinegar, wine, fish sauce, saliva and ear drops. In the real samples, 0.3–0.6% RSD of the IMS response and 93–109% accuracy were obtained.
In this study, a microchip electrophoresis method for simultaneous determination of three frequently used pharmaceutical excipients (methylparaben, propylparaben and erythrosine) was described. ...Anionic zone electrophoresis (ZE) separations were performed on the microchip with contact conductivity detection using a high pH buffer (9.8). Sufficient resolution of the analytes (≥ 2.6) was achieved by 1 mmol L
−1
β-cyclodextrin added to the buffer. Adsorption of the analytes on the walls of a poly(methylmethacrylate) microchip was suppressed by adding 1 mmol L
− 1
sulfate to the sample. The LOD values for the excipients ranged from 0.5 to 11.1 µmol L
− 1
. High repeatability of the migration times of the analytes in model (< 2.9% RSD) and real pharmaceutical (< 4.1% RSD) samples was reached on the microchip. Peak areas of the analytes in all analyzed samples were characterized by RSD values ranging from 0.4 to 5.7%. The ZE method was successfully applied to the analysis of pharmaceutical syrups after a simple pretreatment (centrifugation and dilution), and gave recoveries of the analytes in the range 86.1–96.6%. The results showed a good agreement with those obtained by CZE with UV detection (254 nm) at 95% confidence level.
4-Nonylphenol belongs to the alkylphenol group of chemicals, and its high occurrence in the environment can cause an adverse effect on human health. Breast milk can serve as a marker to take measure ...of human exposure to these chemicals through different routes of exposure. In this work, the influence of selected factors (the kind of water drank by the mothers; the consumption of fish, pork, and beef; wearing gloves; using nail polish, gel nails, vitamins, and medication) on the concentration on 4-nonylphenol in 89 breast milk samples was studied. The concentrations of nonylphenol in breast milk were determined by HPLC with fluorescence detection. The lowest and highest concentrations of 4-nonylphenol in breast milk were 0.97 ng/mL and 4.37 ng/mL, respectively. Statistical significance was observed for the consumption of pork (
= 0.048) and fish (0.041) in relation to the 4-nonylphenol concentration. Certain parameters (use of gel nails, beef consumption, and vitamin supplementation) were at the border of statistical significance (
= 0.06). Other parameters did not show any statistical significance. The results showed that breast milk in Slovakia does not contain a harmful dose of 4-nonylphenol and does not cause health problems. But it is necessary to continue this research and perform extended screening on a larger number of samples.
A capillary isotachophoresis (CITP) method performed in a column-coupling apparatus has been developed for the simultaneous determination of glutathione (GSH) and glutathione disulfide (GSSG) ...concentrations in blood samples. The determination of GSSG and GSH concentrations in biological samples is important because of their roles in oxidative stress. Different concentrations of a leading ion in the coupled columns (concentration cascade) and a large volume (37 µ ) of the injected sample facilitated a GSSG concentration of between 2 and 25 µmol/l. A reaction between iodoacetate and GSH under alkaline conditions was used to prepare the sample in order to avoid oxidation of GSH to GSSG. This step eliminated the main source of systematic errors with regard to the determination of the GSSG concentration. A linear relationship (R2=0.9969) between the zone length of S-(carboxymethyl)glutathione (the product of the reaction between GSH and iodoacetate) and the concentration of GSH (40-120 µmol/l) was obtained. The method was applied to the analysis of bovine blood samples that had been diluted by a factor of ten with satisfactory results
An online combination of isotachophoresis (ITP) and capillary zone electrophoresis (CZE) was employed on a microchip with a column-coupling technology for the determination of homocysteine in various ...body fluids. ITP with its high concentration ability was used as a sample pretreatment and injection technique for CZE, which facilitated the rapid and sensitive determination of homocysteine. The resolution of the analyte from other constituents present in real complex samples was enhanced by discrete spacers, which were added to the injected sample. A solid-phase microextraction (SPME) pretreatment technique based on silver- and barium-form resins was used prior to the ITP-CZE analysis to remove high concentrations of chloride and sulfate naturally present in the analyzed samples. The combination of the micropretreatment and microelectrophoresis techniques facilitated the determination of trace concentrations of homocysteine in samples of urine and saliva
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